Cardiac rhythm management system with optimization of cardiac performance using heart rate

ABSTRACT

A method of optimizing inter-site delay is disclosed for a cardiac rhythm management device that includes a dual chamber pacemaker, especially designed for treating congestive heart failure by pacing a plurality of sites. A microcontroller is operative to adjust the pacing mode and inter-site delay of the pacemaker so as to achieve optimum hemodynamic performance. Atrial cycle lengths measured during transient (immediate) time intervals following a change in the mode inter-site delay are signal processed and a determination can then be made as to which particular configuration yields the optimum performance. Performance is optimized when the patient is at rest and when the patient exercises so that a rate-adapted dynamic value of the optimum performance can be applied.

This application is a divisional application of application Ser. No.09/545,536, filed Apr. 7, 2000.

BACKGROUND OF THE INVENTION

I. Field of the Invention

This invention relates generally to implantable cardiac rhythmmanagement devices, and more particularly to a method for establishingan optimum pacing mode and delay parameters for multiple pacing sites ina dual chamber implantable programmable pacemaker.

II. Related Art

An earlier patent to Baumann, a co-inventor herein, U.S. Pat. No.4,800,471, assigned to the assignee of the present invention, theteachings of which are hereby incorporated by reference, explains thatcardiac pacing can be used to improve hemodynamics in congestive heartfailure (CHF) patients. One recognized and accepted indication ofhemodynamic performance is reflected in the patient's pulse pressure(PP) which is defined as the difference between systolic aortic pressureand diastolic aortic pressure. PP could be used to optimize the pacingparameters in applying CHF therapy, however, this would require the useof a suitably positioned pressure sensor.

The Baumann '471 patent recognizes that an indirect indication of PP canbe derived from the patient's atrial cycle length (ACL), which is theduration of the interval between consecutive P-waves in an ECG signal.The earlier Baumann patent discloses a method for using ACL to optimizeCHF therapy parameters that involves looking at a transient sequence inwhich, after a period of intrinsic cardiac activity, a shortpredetermined sequence of pacing stimuli is delivered to the patient'sheart. Any subsequent transient increase in measured ACL provides anindication of the therapy's effectiveness over intrinsic cardiacactivity. Likewise, a subsequent transient decrease in measured ACL isindicative that the pacing therapy is non-beneficial.

In applying the methodology to an implantable, microprocessor-basedcontroller of the type typically used in a programmable dual-chamberpacemaker, the device is made to cycle through transient paced beatswith different pacing mode and AV delay configurations. Each suchconfiguration is defined to be a group of consecutive beats with thesame paced AV delay and the same pacing mode (right ventricular, leftventricular or biventricular pacing). Each of the configurations isimmediately preceded by a group of baseline beats. In the disclosedarrangement, three different pacing modes and five different AV delaysare used, with each such delay being shorter than a previously measuredvalue of the intrinsic AV delay. The particular mode/AV delaycombination that results in the largest increase in ACL is thenprogrammed into the pacemaker to thereby optimize hemodynamicperformance of the patient's heart. To avoid inaccuracies due to noise,the algorithm described in the Baumann '471 patent is made to vary theorder of therapy; randomization and averaging techniques are then usedto extract data from repeated tests.

While the above approach has proved to be a useful tool, it does nottake into account variations in time between pulse events with respectto pacing at multiple sites. It is common to stimulate both ventriclechambers, for example, and particularly the left ventricle can beprovided with a plurality of sequentially paced sites. Each of these isoperated using a timed delay sequence which may be selected from a menuof sequence timings which itself may change as data regarding patienthistory accumulates. Thus, if all paced sites could be integrated intoan optimal pacing rhythm, additional benefit could be accorded thepatient.

SUMMARY OF THE INVENTION

The foregoing features and advantages of the invention are achieved byproviding an improved method for optimizing the inter-site delay andpacing mode configuration of an implanted, programmable pacemaker whentreating CHF patients. The pacemaker involved is of the dual chambertype that includes an atrial sense circuit, a ventricular sense circuitand a pulse generator for applying cardiac stimulating pulsesselectively to the right ventricular chamber, the left ventricularchamber or both chambers sequentially (biventricular pacing). Aplurality of pacing sites may be located in a single chamber, usuallythe left ventricle, and these are also paced using a time variable delaysequence. The patient's intrinsic atrial depolarization events aretracked and from such events the ACL is measured over a firstpredetermined number of heartbeats, N₁, to establish a baseline value.At least one of the inter-site delay interval and the pacing modeconfiguration is changed for a predetermined number of stimulatedheartbeats, N₂ and, again, the ACLs between successive paced beats ismeasured. These steps are repeated in iterative cycles until all of thepreprogrammed inter-site delay intervals and ventricular chamber optionshave been utilized. Subsequently, a comparison is made to determinewhich configuration of pacing mode and inter-site delay values resultedin the maximum increase ACL and those values are then programmed intothe pacemaker. In that maximum increase of ACL correlates with maximumincrease of PP, hemodynamic performances are thereby optimized.Additional performance parameters may also be used to correlate to PP orother relevant indicators of cardiac performance, these performanceparameters include: ventricular volumes, blood flow velocity, totalacoustic noise, and direct measurement of pressure.

As used herein, the terms “site-to-site delay” and “inter-site delay”mean the time interval between any sequential pacing events in the samecardiac cycle regardless of whether they occur in different or the samechamber. Thus, AV, V—V, V₁–V₂ (same chamber), A—A etc. may berepresented depending on the pacing configuration.

The optimization determination is first made with the patient at rest todetermine the most advantageous pacing mode. Thereafter, a one or moreadditional or periodic determinations can be implemented with thepatient exercising or otherwise in an active state employing thetechnique to determine the optimum site-to-site delays and enabledynamic site-to-site delays to be implemented based on activity level.This empowers the system to implement dynamic site-to-site delays on itsown based on an internal monitoring system.

DESCRIPTION OF THE DRAWINGS

The foregoing features, objects and advantages of the present inventionwill become apparent to those skilled in the art from the followingdetailed description of a preferred embodiment, especially whenconsidered in conjunction with the accompanying drawings in which:

FIG. 1 is a schematic block diagram of a dual chamber pacemakerincorporating a microprocessor-based controller for pacing at aplurality of sites in which the inter-site delay parameters areoptimized in accordance with the algorithms disclosed herein;

FIG. 2 is a schematic block diagram of the microprocessor-basedcontroller incorporated into the pacemaker of FIG. 1;

FIGS. 3A, 3B, 3C, 3D and 3E, when arranged as shown in FIG. 3,illustrate a flow diagram for the optimization algorithm of the presentinvention;

FIG. 4 is a representation of a series of baseline and paced beatsuseful in explaining the development of ACL features in accordance witha first algorithm;

FIG. 5 is a drawing similar to FIG. 4 for a second algorithm; and

FIG. 6 is a plot of one dynamic delay v. cycle length relationship.

DESCRIPTION OF THE PREFERRED EMBODIMENT

The present invention provides a method for establishing an optimumpacing mode and delay parameters for multiple pacing sites in a dualchamber implantable programmable pacemaker. The invention is describedbelow in the context of utilizing atrial cycle length as the measuredparameter for assessing the efficacy of the pacing mode and delayparameters. One skilled in the art will recognize that a variety ofalternative performance parameters may be used to determine the efficacyof the pacing mode and pacing parameter. These performance parametersinclude ventricular volumes, blood flow velocity, total acoustic noise,and direct measurement of pressure.

These performance parameters may be assessed with a number of specificmethods. That is, there are a many ways of assessing cardiac functionincluding systolic function and/or diastolic function of a heart, thatmay be incorporated into an implantable microcontroller based cardiacpacemaker. Thus, for example, the cardiac function sensing circuit maymeasure intracardiac impedance variations due to the influx and outflowof blood from one of the ventricular chambers. This method is discussedin U.S. Pat. Nos. 4,686,987 and 4,674,518 to Salo, which are herebyincorporated by reference. Using this method it is possible to assessventricular volume, stroke volume, cardiac output and derivatives ofthese parameters.

The cardiac function sense circuit may also comprise an accelerometerfor measuring heart sounds or total acoustic noise (TAN). The TANcorresponding to optimal mechanical timing of the heart may be measuredusing an implantable accelerometer as disclosed in U.S. Pat. No.6,044,298 to Salo et al, hereby incorporated by reference. It is alsocontemplated that a micromachined piezoelectric pressure transducer maybe mounted on the right or left ventricular pacing lead where it maymeasure right or left ventricular pressure parameters such asend-diastolic or end systolic pressure or derivatives of these pressurescorresponding to ventricular contractility.

The cardiac function sense circuit may also comprise a Doppler flowmeter having a flow sensor operatively positioned relative to the aortaor pulmonary artery for measuring peak aortic or pulmonic flow velocityfrom which measures that are directly correlated to stroke volume andcardiac output may be derived. Similar measurements may be made ofmitral or tricuspid flow velocity.

Referring now to FIG. 1 representing a preferred embodiment, there isshown enclosed by a dashed-line box 10, a cardiac rhythm managementdevice, here depicted as a VDD bradycardia pacemaker 12, which isadapted to be operatively coupled to a patient's heart by means of aconventional pacing lead 14. In particular, an atrial sensing electrodedisposed in the right atrium of the heart is coupled by a wire 16 in thelead 14 to an atrial sense amplifier 18. Similarly, a ventricularsensing electrode disposed in the right ventricle is connected by a wire20 in the lead 14 to a ventricular sense amplifier 22 contained withinthe pacemaker 12. Thus, when the SA node in the right atriumdepolarizes, the resulting signal is picked up by the atrial senseamplifier 18 and applied to a microprocessor-based controller 24 whichwill be more particularly described with the aid of FIG. 2. Ventriculardepolarization signals (R-waves) are likewise amplified by theventricular sense amplifier 22 and applied as an input to themicroprocessor-based controller 24.

The microprocessor-based controller 24 is connected in controllingrelationship to a pulse generator 26 to cause a ventricular stimulatingpulse to be applied, via conductor 28 in lead 14, to tissue locatedproximate the apex of the right ventricle (RV) to initiate ventriculardepolarization that spreads as a wave across both the right and leftventricles. The pulse generator 26, under control of themicroprocessor-based controller 24, can also be made to applystimulating pulses over a wire 30 in lead 14 to stimulate the heart'sleft ventricle (LV). If the pacing mode calls for biventricular pacing,the pulse generator 26 is controlled by the microprocessor-basedcontroller 24 to deliver stimulating pulses to sites in both the rightand left ventricles (BV). In accordance with contemporary techniques,the left ventricle additionally may be sequentially paced at a pluralityof locations (sites).

The microprocessor-based controller 30 controls the timing ofstimulating pulses at cardiac sites relative to a selected precedingdepolarization signal and to each other to thereby define site-to-sitepulsing intervals. The system is capable of pacing in several modes andat variable site-to-site time delays in each mode.

An external programmer 32 is arranged to send data signalstranscutaneously to the implanted pacemaker 12 and also to receivesignals originating within the pacemaker. In this fashion, a physicianis capable of programming such parameters as pacing rate, pacing pulsewidth, pacing pulse amplitude, sensitivity, AV delay interval, etc., ina fashion known in the art. The external programmer may also be used toreceive signals and pass them on to an external monitor (not shown)incorporating a microprocessor and associated memory.

FIG. 2 shows a more detailed block diagram of the microprocessor-basedcontroller 24 shown in FIG. 1. It is conventional in its architectureand includes a microprocessor chip 34 and associated RAM and ROM memorymodules 36 and 38 connected to it by an address bus 40 and a data bus42. As is known in the art, the RAM memory 36 is a read/write memorycomprising a plurality of addressable storage locations where multi-bytedata words and operands used in the execution of one or more programsmay be stored for subsequent readout. The ROM memory 38 will typicallybe used to store the control programs executable by the microprocessorchip 34.

Also connected to the address bus and data bus is an I/O interfacemodule 44. If a separate analog-to-digital converter, as at 46, isutilized rather than an on-board A/D converter forming a part of themicroprocessor chip 34, its output will be connected through the I/Omodule 44 allowing the analog outputs from the atrial sense amplifier 18and the ventricular sense amplifier 22 to be digitized before beingrouted to the microprocessor chip 34. If the particular microprocessoremployed incorporates an on-board A/D converter (as is somewhatconventional), then the outputs from the A-sense amplifier 18 andV-sense amplifier 22 are applied directly to appropriate inputs of themicroprocessor chip 34.

Also coupled to the I/O module 44 is a transceiver 48 that is used tointerface the external programmer 32 to the implanted pacer 12. Themanner in which an external programmer appropriately placed on the chestwall in proximity to the implanted device is capable of transmittingdigitally encoded data therebetween is well known to those skilled inthe pacemaker art.

FIGS. 3A, 3B, 3C, 3D and 3E when arranged as shown in FIG. 3 comprise aflow chart of the algorithms executed by the microprocessor 34 inarriving at an optimal pacing mode and inter-site delay combination fora patient in which the system of the present invention is implanted.

Before explaining the steps of the algorithm in detail, a brief overviewof the methodology is deemed helpful.

The algorithms can be executed by the microprocessor-based controller inthe pacer or in an external microprocessor in the monitor/programmer 32.In the following description, it is assumed that the control algorithmsare executed by the microprocessor 34 in the implanted device. Thealgorithms, using cardiac atrial cycle lengths measured in the VDDpacemaker, determines a patient's optimum pacing mode and inter-sitedelay configuration, which is the mode (e.g., RV, LV, BV, RV and LV₁,LV₂, etc.) and inter-site delay during VDD pacing which maximizescardiac function (e.g., PP) for the patient. The pulse generator 26 isthen set to operate at this optimum pacing mode and inter-site delay.

The optimal pacing mode and associated optimum inter-site delays aredetermined from the maximum (or minimum) value of one of severalempirically derived features which are calculated from the atrial cyclelengths. In particular, the atrial cycle lengths immediately following atransition from an intrinsic or paced baseline (BL) to a paced mode,inter-site delay, i.e., during a transient period of the paced mode andinter-site delay, is used. Thus, this invention eliminates the need fora period of waiting for hemodynamic stability to be reached during thepaced mode and particular inter-site delay.

The pulse generator will be made to cycle through a predetermined numberof intrinsic or paced BL beats followed immediately by paced beats usinga first mode and inter-site delay configuration, followed immediately byadditional intrinsic or paced BL beats, followed immediately by beats ofa second mode and inter-site delay configuration, etc., until all of thepossible programmed configurations have been utilized. The ACL betweensuccessive beats is computed and stored as an array in the RAM memory ofthe microprocessor-based controller.

Once the array of ACL values are stored, they are subsequently processedto arrive at values of ACL features. In particular, the array of valuesmay be smoothed using a 3-point moving rectangle window or an 11-pointmoving Blackman window. Then for each configuration and repeatedinstances thereof, further computations are made to identify theparticular configuration exhibiting the largest average of the smoothedACL features. It is this configuration that is determined to be theoptimum and the pacemaker is then set to operate in this optimumconfiguration. The automatic selection of optimal mode delay which isfound to optimize cardiac function eliminates any need for manualprogramming of the implanted pacemaker by the physician.

The algorithms of the present invention are based upon a hypothesis thatif a transient change in atrial cycle length is large positive, then thetransient change in aortic pulse pressure is also large positive. Thus,the largest positive change in atrial cycle length predicts the largestpositive change in aortic pulse pressure.

There is a physiological basis for this relationship. A large, suddenincrease in the aortic pressure (in this case due to the sudden changefrom baseline cardiac function to paced mode inter-site delay cardiacfunction) is sensed by arterial barroreceptors, and the reflex mechanismof the Autonomic Nervous System (ANS) tries to drive the aortic pressureback to its previous stable (in this case, baseline) value by increasingthe atrial cycle length. The ANS acts as a negative feedback controlsystem for the aortic pressure.

The paced mode and inter-site delay associated with the largest meanincrease in ACL is hypothesized to be the optimum paced mode andinter-site delay for the pacemaker. The optimum is the one that providesa maximum increase in aortic pressure over baseline aortic pressure forthe then-current state of activity of the patient. As will also be seen,this may change with increased levels of activity in the patient.

With the foregoing summary in mind, then, attention is directed to theflow charts of FIGS. 3A through 3D. The first step in the algorithm isto derive a baseline. The pulse generator is initially inhibited whileintrinsic cardiac activity is sensed such that a value of the patient'sintrinsic AV delay and ACL can be measured. Next, the physician maygenerate a list of all possible combinations of three pacing modes and apredetermined number of inter-site delay values where each of the delayvalues is set as desired. While a different number of paced inter-sitedelay values can be selected, arbitrarily and for purposes ofexplanation of the inventive algorithm, it will be assumed that fivedifferent inter-site values are established by the physician. These mayinclude a plurality of pacing sites in the same chamber and/or sites inseveral chambers. Generally, plural sites will be limited to the leftventricle, however. This leads to 3×5=15 possible configurations asindicated in block 52.

To avoid any influence that the particular order in which theconfigurations are employed in pacing the patient, the list generated instep 52 is randomized as reflected in block 54 in FIG. 3A.

Again, without limitation, a string of beats with the pulse generatorinhibited may be used to establish BL and then for each of thesebaseline beats, the atrial cycle length between them is determined. Asearlier mentioned, rather than using intrinsic inter-site delays toestablish BL, the BL can also be at a particular configuration of pacingmode and inter-site delays. In the description to follow, a group of atleast 15 sequential beats are generated. The ACL measurement may beperformed in the microprocessor by initiating a timer upon theoccurrence of a P-wave in the cardiac electrogram and stopping the timerupon detection of the next succeeding P-wave. The ACL value associatedwith each BL beat is then stored as an array in the RAM memory 36.

Referring again to the block diagram of FIG. 3A, immediately followingthe last of the beats used in establishing BL, the heart is paced usinga selected configuration drawn from the randomized list developed atblock 54. Again, without limitation, the second number of beats mayequal five. As with the BL beats, the ACL for the paced beats is alsodetermined as reflected in block 58.

A test is next made at block 60 to determine whether all of the 15possible configurations on the randomized list have been used and theACL values associated therewith stored in the memory.

If not all of the configuration possibilities have been exhausted,control returns over path 61 to block 56 and the operations reflected inblocks 56 and 58 are repeated until all of the possibilities have beenexhausted. So that any anomalies which may have occurred in themeasurement of the respective ACL values can be averaged out, steps 54,56, 58 and 60 are repeated a predetermined number of times, e.g., fivetimes, to obtain additional instances of the configurations that canlater be averaged. See decision block 62.

The change in PP caused by the five paced beats in step 58 is immediate.There is no time delay. However, the change in ACL caused by the reflexmechanism of the Autonomic Nervous System in response to this change inPP is not immediate. There is a time delay of several beats. Thus, thedelayed change in ACL can occur during the 15 BL beats in step 56 whichfollow the five paced beats in step 58. Thus, the final 15 or more BLbeats in step 64 are needed to follow the final five paced beats in step58.

Once the raw ACL values have been computed and stored as an array in theRAM memory, further algorithms may be used to process the raw data inarriving at the particular pacing mode-AV delay configuration yieldingoptimum hemodynamic performance.

Algorithm 2 shown on FIG. 3C is executed to first select candidates forbeing the optimum configuration of pacing mode and inter-site delays.Here at block 77, the raw ACL data (or VCL data) are first smoothedusing a known signal processing approach referred to as an 11 pointmoving Blackman window which yields a smoothed ACL array, (sACL). Atblock 78, a determination is made as to whether any abnormal beats,e.g., PVCs, occurred during an interval from eight beats before thefirst transient pace beat to 8 beats after the last transient pacedbeat. If abnormal beats are detected, the collected data is defined tobe an “invalid instance”. If no such abnormal beats occurred, it isdefined to be a “valid instance”. Next, and as reflected by block 79,for each configuration, a determination is made as to whether less thanthree “valid instances” occurred and, if so, it is defined to be an“invalid configuration”. On the other hand, if three or more validinstances occur, it is defined to be a “valid configuration”.

Next, as indicated by block 80, for each valid instance of a validconfiguration, a determination is made as to the maximum value of sACLvalues in an interval from two beats after the first beat of aconfiguration instance to eight beats after the first beat of theconfiguration instance. Likewise, a minimum value of sACL values in aninterval from three beats before the first beat of the configurationinstance to the beat with the maximum value is determined. FIG. 5 ishelpful in defining the respective intervals in which the maximum valuesand minimum values are to be found. Once the maximum value and minimumvalue in the respective intervals have been determined, a smoothed ACLfeature value, referred to in the flow charts by the acronym sACLf, iscomputed as the maximum value minus the minimum value.

Upon completion of step 80, for each of the valid configurations of modeand inter-site delays, the mean of the sACLf values over the number ofvalid instances of a given configuration is computed. See block 82.Next, out of the previously determined valid configurations, theconfiguration exhibiting the largest mean sACLf is computed (block 84).

Once the particular configuration exhibiting the largest mean sACLf isdetermined, via step 84, the number of valid instances where theparticular valid configuration has been repeated are examined todetermine a median value and a maximum value of the smoothed ACLfeature, sACLf. With the median and maximum values so determined, a testis made to determine whether the quantity (MAX/MEDIAN−1) is less than apredefined threshold. The purpose of this threshold test is to remove aMAX whose value is too large (relative to the median value). The“predefined threshold” has been determined empirically from dataaccumulated from a significant number of patients as a value of 9.5,which gave good results for the set of patients investigated.

If the result of the test is true, a potential candidate for the optimumconfiguration has been found (block 88). However, if the test at block86 had proved false, the instance with the maximum value of sACLf isdefined to be an invalid instance. If this valid configuration now hasless than three valid instances, then it is defined to be an invalidconfiguration. If the valid configuration has three or more validinstances, the mean of values of valid instances are calculated for thevalid configuration. Control then loops back over line 91 to block 84 toagain repeat steps 84 and 86 until such time as the test set out inblock 86 comes out “true”.

Referring again to the flow diagram of FIG. 3A, after all candidates forthe optimum configuration have been determined, further processing takesplace to determine which of the candidates is the optimum configurationso that the pacemaker can be programmed to operate in thisconfiguration. Specifically, a test is made at block 92 to determinewhether the largest mean sACLf computed at block 82 is less than 8.1milliseconds. If it is, algorithm 1 of FIG. 3B is executed. If not, afurther test is made to determine whether the largest mean sACLf valueis greater than 29.0 milliseconds. If so, algorithm 3 illustrated atFIG. 3D is executed. If the largest mean sACLf feature value liesbetween 8.1 milliseconds and 29.0 milliseconds, it is the optimumconfiguration and, as indicated by block 96, the pacemaker is programmedto operate with that configuration of pacing mode and AV delay. The 8.1ms and 29.0 ms values have been empirically established by study of dataobtained from a set of ten patients in a study.

Referring next to FIG. 3B, the details of Algorithm 1 will be furtherexplained. The first step in Algorithm 1 is identified by block 66 andinvolves smoothing the array of ACLs with a 3-point moving rectanglewindow. The resulting sACLf values are then also stored in the RAMmemory. While other smoothing techniques are known to persons skilled insignal processing, a 3-point moving rectangle moving technique proves tobe simple to execute and produces reliable results.

As was the case with algorithm 2, tests are made to determine whetherany abnormal beats occurred in the interval from 8 beats before a firstpaced transient beat to 8 beats after the last paced transient beat foreach of the configuration instances and if such an abnormal beat didoccur, that configuration instance would be determined to be invalid.Then, each configuration is examined to determine if three or more validinstances were found in that configuration and, if so, it would bedefined to be valid. However, if a configuration was found to includeless than three valid instances, it would be defined as an invalidconfiguration.

Next, and as is reflected by block 68 in the flow diagram of FIG. 3B,for each valid instance of each valid configuration, the maximum valueand the minimum value of the smooth ACL in an interval from two beatsafter the first beat of the configuration instance to seven beats afterthe first beat of the configuration instance are computed. Thisoperation is further explained with the aid of FIG. 4. In FIG. 4, thereis shown a series of 15 baseline beats, followed by five paced beats ofan instance of a first configuration identified as C, again followed byanother series of 15 baseline beats. The interval in which the maximumand minimum values of smoothed ACLs are to be located is labeled “MAXand MIN”. Likewise, the interval in the which the mean value of thesmoothed ACLs is to be located is identified by “MEAN”. By selecting theintervals in the manner indicated, changes in ACL of a transient natureas distinguished from steady state is guaranteed. Once the MAX and MINvalues of sACL for the configuration instance are known, a test is madeto determine whether the absolute value of the quantity (MAX−MEAN) isgreater than the absolute value of the quantity (MIN−MEAN) for theconfiguration instance. If the outcome of the test is true, then thesmoothed ACL feature (sACLf) for the configuration instance isdetermined to be the quantity (MAX−MEAN). If the test is false, thensACLf is made to be (MIN−MEAN). See steps 70 and 72 in block 68.

Next, as is indicated by operation block 74, for each of the validconfigurations, a computation is made to determine the average or meanof the sACLf over the number of valid instances of that configuration.Once the operation indicated by block 74 has been completed, theparticular valid configuration exhibiting the greatest mean of smoothedACL features is identified, as the pacemaker is automatically programmedto operate with this optimum configuration. See block 76.

Referring again to FIG. 3A, if the test at block 94 had established thatthe largest mean sACLf had been greater than 29.0 milliseconds,algorithm 3 shown in FIG. 3D would have been executed rather thanalgorithm 1. Referring to FIG. 3D, the steps therein are substantiallyidentical to those of algorithm 2 shown in FIG. 3C except that in block97 of FIG. 3D corresponding to block 80 in FIG. 3C, the maximum value ofsACL (or sVCL) is determined at an interval of from one beat after thefirst beat of a configuration instance rather than from two beats aftera first beat configuration instance. Secondly, block 100 in algorithm 3shown in FIG. 3D differs from block 88 of algorithm 2 shown in FIG. 3Cin that rather than identifying a candidate optimum configuration, theactual optimum configuration is established and the pacemaker is thenprogrammed to operate in this optimum configuration.

The above optimization is designed to be accomplished when the patientis asleep or otherwise in a sedentary state. The optimization algorithm,however, is also useful in optimizing pacing of the same individualduring physical activities. This is illustrated in the flow diagram ofFIG. 3E which differs from FIG. 3A only slightly. First, a determinationis made at 49 based on intrinsic ACL or VCL (indicative of HR) as towhether the patient is exercising or at rest after a number of intrinsicbeats are sensed. If the rate exceeds a predetermined limit, it ispresumed that the patient is exercising. If it is determined that thepatient is exercising, the algorithm of FIG. 3E is completed: otherwisethe program ends at 50. The only difference in the determination in thissituation is that the optimum pacing mode determined when the patientwas at rest is retained and only the inter-site time delays are cycledand adjusted based on activity state. The result obtained yields anoptimum dynamic value of the inter-site delays.

In accordance with one aspect of the invention, and in addition to theabove, it has been found that in bi-ventricular pacing dynamicinter-site delay adjustments may be made on a beat-by-beat basis basedon a linear function of the VCL or ACL. This relationship may berepresented by the relation:

d_(vv) = m i_(vv) + b$m = \frac{d_{\max} - d_{\min}}{i_{lrl} - i_{url}}$b = d_(max) − m i_(lrl)

where

-   -   i_(lrl) and i_(url) are the lower and upper rate limit        intervals, the lower and upper rate limits having been set by        the physician;    -   d_(max) and d_(min) are the maximum and minimum interventricular        delays for sequentially paced sites, one in each ventricle,        which are also set by the physician based on the relative        activity of the patient over time and which may be varied based        on statistical activity trends of the patient;    -   i_(vv) is the ACL (VCL could also be used);    -   d_(vv) is the dynamic interventricular delay or the delay        between sequentially paced sites, one in each ventricle.

In this manner, the d_(vv) inter-site delay can be caused to varylinearly with the ventricular cycle length (or ACL). This is illustratedby the plot of FIG. 6. Alternatively, it is contemplated that anon-linear function may be used.

Thus, in accordance with the invention, patient tests have shown thatthe relatively easy-to-measure atrial cycle length (or ventricular cyclelength) can be used to automatically determine the pacing mode andsite-to-site delay configuration which provides pulse pressures greaterthan the pulse pressure achieved with baseline cardiac performance. Theneed for a special sensor to actually measure pulse pressure itself,which is difficult to measure, is eliminated.

This invention has been described herein in considerable detail in orderto comply with the patent statutes and to provide those skilled in theart with the information needed to apply the novel principles and toconstruct and use such specialized components as are required. However,it is to be understood that the invention can be carried out byspecifically different equipment and devices, and that variousmodifications, both as to the equipment and operating procedures, can beaccomplished without departing from the scope of the invention itself.As already mentioned, the intrinsic and paced beat information canreadily be telemetered out to an external programmer/monitorincorporating a microprocessor and associated memory so that the ACLdeterminations and signal processing thereof can be done external to thepatient in arriving at the optimal pacing mode-AV delay interval. Hence,the scope of the invention is to be determined from the appended claims.

1. A method of optimizing the inter-site delay and pacing modeconfiguration of a dual chamber pacemaker of the type having means forsensing atrial depolarization events, means for sensing ventriculardepolarization events and means for applying cardiac stimulating pulsesselectively to a plurality of sites including at least one chamber witha plurality of sites within said chamber, said sites at locationsselected from the right, left or both ventricular chambers atpredetermined intersite delay intervals following detection of atrialdepolarization events, comprising the steps of: (a) tracking a patient'sintrinsic ventricular depolarization events; (b) measuring the patient'sventricular cycle length (VCL) between successive ventriculardepolarization events over a first predetermined number of heart beats,N₁, and storing the measured VCLs as an array in a memory to establish abaseline value; (c) changing at least one delay interval and pacing modeconfiguration by changing, for a second predetermined number of heartbeats, N₂, less than the first predetermined number of heart beats, (i)one or more intersite delay intervals from a set including at least onedelay interval between said plurality of sites in said at least onechamber of the pacemaker from the baseline value to a different delayinterval; (ii) the sites to which the stimulating pulses are applied;(d) measuring the patient's VCLs between successive ventriculardepolarization events over the second predetermined number of heartbeats and storing the measured VCLs in the array in said memory; (e)calculating and storing a VOL feature value obtained from the patient'sventricular cycle length measured in steps (b) and Cd); (f) repeatingsteps (a)–(e) in iterative cycles over a range of inter-site delayintervals and ventricular chamber(s) selected for receiving the cardiacstimulating pulses; (g) after step (f) for each pacing mode intersitedelay configuration calculating the average of the VCL features over allof the occurrences of the configuration; (h) determining the optimalconfiguration from among the averages determined in step (g); and (i)setting the inter-site delay and pacing mode configuration of thepacemaker to the optimal inter-site delay and pacing mode configurationestablished in step (h).
 2. A method as in claim 1 wherein the VCLfeature value is calculated by the steps of: (j) smoothing the array ofVCLs; (k) determining from the smoothed array of VOLs a maximum valueand a minimum value in a first predetermined interval measured in beatsfor each intersite delay and pacing mode configuration; (l) determiningfrom the smoothed array a mean value of VCLs in a second predeterminedinterval measured in beats for each inter-site delay and pacing modeconfiguration; (m) computing an absolute value of the difference betweensaid maximum value and said mean value and computing an absolute valueof the difference between said minimum value and said mean value; (n)comparing the absolute value of the difference between the maximum valueand the mean value with the absolute value of the difference between theminimum value and the mean value to determine which is the larger; and(o) setting the VOL feature value to the difference between the maximumvalue and the mean value when the absolute value of that difference isgreater than the absolute value of the difference between the minimumvalue and the mean value, and setting the VCL feature value to thedifference between the minimum value and the mean value when theabsolute value of the difference between the maximum value and the meanvalue is less than or equal to the absolute value of the differencebetween the minimum value and the mean value.
 3. A method for optimizinginter-site delay intervals and pacing mode configuration of aprogrammable, dual-chamber, cardiac pacemaker of the type having meansfor sensing atrial and ventricular depolarization events, including amicroprocessor-based controller using a plurality of pacing sitesincluding at least one chamber with a plurality of sites within saidchamber, said controller selectively stimulating the right, the left orboth ventricular chambers with pacing pulses at predetermined inter-sitedelay intervals following detection of atrial depolarization events, themicroprocessor-based controller having means for determining ventricularcycle lengths (VCLs) and a memory for storing data in an addressablearray, comprising the steps of: (a) storing in the memory a listing ofpacing mode and inter-site delay configurations, which includes anintersite delay between said plurality of sites within said at least onechamber each such configuration specifying ventricular chamber(s) to bestimulated and an inter-site delay interval to be utilized; (b) pacingthe ventricular chamber(s) in accordance with a pacing mode inter-sitedelay configuration selected randomly from said listing for a firstnumber of beats, N₁, following a second number of intrinsic beats, N₂,sufficient to establish a baseline; (c) repeating step (b) for eachpacing mode and AV delay configuration contained in the listing; (d)determining the VCL values between each of the N₁ and N₂ beats resultingfrom steps (b) and (c) and storing said VCL value in the addressablearray in the memory; (e) repeating steps (b) through (d) a predeterminednumber of instances, N₃; (f) smoothing the array of VCLs; (g)determining for all N₃ instances of each pacing mode and inter-sitedelay configuration the maximum value of the smoothed VCLs in a firstinterval beginning after a change to the first number of beats, N₁, andending after a change to the second number of beats, N₂, and a minimumvalue of the smoothed VCLs in a second interval beginning apredetermined number of beats prior to a change from the n₂ beats to theN₁ beats and ending with the beat associated with the maximum value; (h)computing a smoothed VCL feature as the difference between the maximumvalue and the minimum value; (i) calculating the mean value of thesmoothed VCL features computed in step (h) over the N₃ instances foreach pacing mode inter-site delay configuration and determining theconfiguration yielding the largest mean value; (j) determining among theN₃ instances associated with the configuration yielding the largest meanvalue a median value and a maximum value of smoothed VCL feature; and(k) programming the pacemaker to the configuration determined in step(i) when the difference between the ratio of maximum value and theminimum value is less than a predetermined value.
 4. A method as inclaim 3 and when the ratio of maximum value and the median value ofsmoothed VCL features is greater than or equal to the predeterminedthreshold value, repeating steps (i) and (j) after recalculating themean of the instances of the configuration associated with the largestmean value of smoothed VCL features after removing the instance havingthe maximum value of smoothed VCL features from the instances.
 5. Amethod for optimizing inter-site delay intervals and pacing modeconfiguration of a programmable, dual-chamber, cardiac pacemaker of thetype having means for sensing atrial and ventricular depolarizationevents, including a microprocessor-based controller using a plurality ofpacing sites including at least one chamber having a plurality of siteswithin said one chamber, said controller for selectively stimulating theright and left ventricular chambers with pacing pulses at predeterminedinter-site delay intervals including between said plurality of siteswithin said one chamber following detection of atrial depolarizationevents, the microprocessor-based controller having means for determiningatrial cycle lengths (ACLs) or ventricular cycle lengths (VCLs) and amemory for storing data in an addressable array, comprising the stepsof: (a) establishing an upper rate limit and a lower rate limit forpacing and storing these in memory; (b) establishing a range ofallowable delay intervals between pacing the right ventricle and pacinga first site in the left ventricle in relation to said upper rate limitand said lower rate limit; and (c) making dynamic inter-site delayinterval adjustments to optimize the interval based on a linearrelationship between the delay interval between adjacent pulses in theright and left ventricles and the VCL or ACL, wherein said inter-sitedelay interval is adjusted between maximum and minimum values in saidrange of allowable delay intervals.
 6. A method as in claim 5 whereinsaid linear relationship may be made on a beat-bybeat basis based on alinear function of the VCL or ACL.
 7. A method as in claim 6 whereinsaid linear function is represented by the relation:d_(vv) = m i_(vv) + b$m = \frac{d_{\max} - d_{\min}}{i_{lrl} - i_{url}}$b = d_(max) − m i_(lrl) where i _(lrl) and i _(url) are the lower andupper rate limit intervals, the lower and upper rate limits; d_(max) andd_(min) are the maximum and minimum interventricular delays forsequentially paced sites, one in each ventricle; i_(vv) is the ACL orVCL; d_(vv) is the dynamic interventricular delay or the delay betweensequentially paced sites, one in each ventricle.
 8. A method as in claim7 including the step of setting d_(max) and d_(min) based on therelative activity of the patient over time.
 9. A method for optimizingatrioventricular delay, comprising: (a) tracking an intrinsicperformance parameter of a patient's heart; (b) measuring a performanceparameter over a first predetermined number of heart beats, N₁, a firstset of inter-site delay intervals said set including at least one delayinterval from at least one chamber having a plurality of sites thereinand an inter-site delay interval therebetween and storing the measuredperformance parameter as an array in a memory to establish a baselinevalue; (c) changing at least one of one or more inter-site delayintervals and pacing mode configuration for a second predeterminednumber of heart beats, n₂, less than the first predetermined number ofheart beats by changing the delay interval of the pacemaker betweensuccessive sites from the baseline value to a different delay interval;(d) measuring the patient's performance parameter between successiveatrial depolarization events over the second predetermined number ofheart beats and storing the measuring performance parameter in the arrayin said memory; (e) calculating and storing an performance parameterfeature value obtained from the patient's performance parameter measuredin steps (b) and (d); (f) repeating steps (a)–(e) in iterative cyclesover a range of intersite delay intervals; (g) after step (e) for eachpacing mode inter-site delay configuration calculating the average ofthe performance parameter features over all of the occurrences of theconfiguration; (h) determining the optimal configuration from among theaverages determined in step (f); and (i) setting the inter-site delaysand pacing mode configuration of the pacemaker to the optimal inter-sitedelays and pacing mode configuration established in step (g).
 10. Amethod as in claim 9 wherein the performance parameter is selected fromthe group consisting of ventricular volumes, blood flow velocity, totalacoustic noise, and direct measurement of pressure.